Preliminary indications that recombinant human IL-16 attracts and stimulates lymphocytes of the amphibian, Xenopus laevis implying an ancestral role for CD4 as a cytokine receptor

Gillis, Jacob E.; Uccello, Taylor P.; Magri, Zoie; Morris, Nicole; Maniero, Gregory D.

doi:10.1016/j.cyto.2020.155254

Cited by 6 publications

(14 citation statements)

References 48 publications

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“…IL-16 is a cytokine that is found ubiquitously throughout vertebrate phylogeny and has been described not only in humans but in a variety of mammals [20], birds [23][24][25][26], fish [27,28]. IL-16 has even been described in invertebrates [29][30][31] Additionally, inferred protein sequences from genetic data can be found for IL-16 and pro-IL16 in amphibians and reptiles [32]. The sequence and structure of IL-16 and pro-IL-16 show considerable homology among disparate vertebrate groups [13,32,33].…”

Section: Il-16 Is An Ancient and Ubiquitous Cytokinementioning

confidence: 99%

“…IL-16 has even been described in invertebrates [29][30][31] Additionally, inferred protein sequences from genetic data can be found for IL-16 and pro-IL16 in amphibians and reptiles [32]. The sequence and structure of IL-16 and pro-IL-16 show considerable homology among disparate vertebrate groups [13,32,33]. In mammals, IL-16 is highly conserved among humans, mice, and African green monkeys at the structural and genetic levels [6,16].…”

Section: Il-16 Is An Ancient and Ubiquitous Cytokinementioning

confidence: 99%

Section: Conservation Of Cd4mentioning

confidence: 99%

“…CD4 is highly conserved in mammals, yet the primary and secondary structures vary considerably among vertebrates [32,38]. In the distal, D1 region, the canonical MHC class II-binding motif of FLXK is found on all eutherian mammals that have been studied [32,38]. However, even though all gnathostomes demonstrate CD4-dependent Th-activity, the D1 region is not highly conserved among representatives of disparate vertebrate groups [32,38].…”

Section: Conservation Of Cd4mentioning

confidence: 99%

“…In the distal, D1 region, the canonical MHC class II-binding motif of FLXK is found on all eutherian mammals that have been studied [32,38]. However, even though all gnathostomes demonstrate CD4-dependent Th-activity, the D1 region is not highly conserved among representatives of disparate vertebrate groups [32,38]. Most non-mammalian vertebrates do not possess the classic FLXK MHC class II-binding motif seen in mammals [32] yet rely heavily on traditional T-helper activity, suggesting that the role of CD4 binding to classical MHC molecules is an important function that has arisen on multiple occasions in vertebrate evolution.…”

Section: Conservation Of Cd4mentioning

confidence: 99%

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Evolutionary Conservation of the Role of CD4 as a Receptor for Interleukin-16

Maniero¹

2021

Interleukins - The Immune and Non-Immune Systems’ Related Cytokines

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The interaction of CD4 with MHC class II during helper T-cell activation and effector function is required for the initiation of an adaptive immune response in all gnathostomes. CD4 is comprised of four immunoglobulin domains but most likely arose from an ancestral two-domain homolog. The distal, D1 domain of CD4 binds to non-polymorphic regions of the MHC molecule, but despite the absolute requirement for this interaction, the sequence and structure of this domain are not well conserved through phylogeny. Conversely, the proximal, D4 domain of CD4 contains the binding site of the cytokine IL-16 and is highly conserved in its amino acid structure. IL-16 is a cytokine that has been described in a wide variety of invertebrate and vertebrate species. The CD4-binding residues on IL-16 are highly conserved throughout phylogeny, allowing for promiscuous binding of IL-16 to CD4 between members of unrelated taxa. This chapter aims to present structural, and functional support for the hypothesis that the CD4 co-receptor of the TCR arose from a primordial receptor for IL-16.

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Section: Il-16 Is An Ancient and Ubiquitous Cytokinementioning

confidence: 99%

Section: Il-16 Is An Ancient and Ubiquitous Cytokinementioning

confidence: 99%

Section: Conservation Of Cd4mentioning

confidence: 99%

Section: Conservation Of Cd4mentioning

confidence: 99%

Section: Conservation Of Cd4mentioning

confidence: 99%

See 3 more Smart Citations

Evolutionary Conservation of the Role of CD4 as a Receptor for Interleukin-16

Maniero¹

2021

Interleukins - The Immune and Non-Immune Systems’ Related Cytokines

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Hyperalgesic Effect Evoked by il-16 and its Participation in Inflammatory Hypernociception in Mice

González-Rodríguez,

Sordo-Bahamonde,

Álvarez-Artime

et al. 2024

J Neuroimmune Pharmacol

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The systemic administration of interleukin-16 (IL-16, 3–30 ng/kg) induced thermal hyperalgesia in mice, that was prevented by the acute injection of an anti-CD4 antibody (1 µg/kg), the depletion of circulating white blood cells by cyclophosphamide or the specific reduction of circulating CD4+ cells provoked by a high dose of an anti-CD4 antibody (30 µg/mouse, 24 h before). IL-16-induced hyperalgesia was locally inhibited after intraplantar (i.pl.) administration of the non-selective cyclooxygenase (COX) inhibitor diclofenac, the COX-1 inhibitor SC-560, the COX-2 inhibitor celecoxib, the TRPV1 antagonist capsazepine or the TRPA1 antagonist HC030031, thus demonstrating that prostaglandins and TRP channels are involved in this effect. The i.pl. administration of low doses of IL-16 (0.1–1 ng) evoked local hyperalgesia suggesting the possibility that IL-16 could participate in hypernociception associated to local tissue injury. Accordingly, IL-16 concentration measured by ELISA was increased in paws acutely inflamed with carrageenan or chronically inflamed with complete Freund´s adjuvant (CFA). This augmentation was reduced after white cell depletion with cyclophosphamide or neutrophil depletion with an anti-Ly6G antibody. Immunofluorescence and flow cytometry experiments showed that the increased concentration of IL-16 levels found in acutely inflamed paws is mainly related to the infiltration of IL-16+ neutrophils, although a reduced number of IL-16+ lymphocytes was also detected in paws inflamed with CFA. Supporting the functional role of IL-16 in inflammatory hypernociception, the administration of an anti-IL-16 antibody dose-dependently reduced carrageenan- and CFA-induced thermal hyperalgesia and mechanical allodynia. The interest of IL-16 as a target to counteract inflammatory pain is suggested. Graphical Abstract

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A teleost interleukin-16 is implicated in peripheral blood leukocytes recruitment and anti-bacterial immunity

Chen

Zhang

et al. 2021

International Journal of Biological Macromolecules

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Preliminary indications that recombinant human IL-16 attracts and stimulates lymphocytes of the amphibian, Xenopus laevis implying an ancestral role for CD4 as a cytokine receptor

Cited by 6 publications

References 48 publications

Evolutionary Conservation of the Role of CD4 as a Receptor for Interleukin-16

Evolutionary Conservation of the Role of CD4 as a Receptor for Interleukin-16

Hyperalgesic Effect Evoked by il-16 and its Participation in Inflammatory Hypernociception in Mice

A teleost interleukin-16 is implicated in peripheral blood leukocytes recruitment and anti-bacterial immunity

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